反应详情

温度

90 °C

To a rubber-septum-capped vial containing 4,6-dichloro-2-morpholinopyrimidine (0.2 M in dioxane, 0.25 mL) and 1-(3-trifluoromethyl-pyridin-2-yl)-piperazine (0.2 M in dioxane, 0.28 mL) (Oakwood Products, Inc., West Columbia, S.C.) add aqueous K3PO4 (0.5 M, 0.125 mL). Heat the mixture at 90° C. for 24 hours. After cooling, add 3-chloro-4-fluorophenylboronic acid (0.2 M in dioxane, 0.35 mL) and K3PO4 (0.5 M in water, 0.10 mL) and flush the vial with argon. Add Pd(PPh3)4 (0.01 M in toluene, 0.125 mL). Heat the mixture at 80° C. overnight, add EtOAc(0.5 mL), separate the organic phase and load onto a 6-mL cartridge containing 1 g of SCX (a sulfonic acid-pregnated silica gel strong cation exchanger). Wash the SCX cartridge with 5 mL of MeOH and elute the product with 10% Et3N in EtOAc (5 mL). Concentrate the eluent to give the pure product which can be converted to the HCl salt: LCMS (m/e); 523, 1H NMR (CDCl3); d 3.4 (br s, 4 H), 3.8 (br s, 4 H), 4.0 (br s, 8 H), 6.4 (br s, 1H), 7.1 (br s, 1H), 7.2 (br s, 1H), 7.9 (m, 3 H), 8.5 (s, 1H).

1. temperatureAfter cooling
2. customflush the vial with argon
3. temperatureHeat the mixture at 80° C. overnight
4. additionadd EtOAc(0.5 mL)
5. customseparate the organic phase and load onto a 6-mL cartridge
6. additioncontaining 1 g of SCX (a sulfonic acid-pregnated silica gel strong cation exchanger)
7. washWash the SCX cartridge with 5 mL of MeOH
8. washelute the product with 10% Et3N in EtOAc (5 mL)
9. concentrationConcentrate the eluent
10. customto give the pure product which